Comparison of intracoronary vs. intravenous administration of abciximab in coronary stenting.

There have been animal and human studies looking at intracoronary (IC) use of abciximab with good short-term clinical outcomes. There exists no data comparing intracoronary with intravenous (IV) administration of abciximab beyond 30 days. We compared the clinical outcomes between the IC (n = 101) and IV (n = 72) group of patients. Patients who had coronary stenting and received abciximab were included in the study. All the patients received the standard systemic bolus dose of abciximab 0.25 mg/kg either via the IC or IV route, followed by a 12-hr IV infusion at 0.125 microg/kg/min. The 6-month composite endpoint of death or myocardial infarction was slightly higher in the IV (13.9%) than in the IC group (5.9%; P = 0.04). The frequency of bleeding complications was similar in both groups. The IC bolus route of abciximab may be superior to the intravenous route. Prospective randomized trials are warranted to validate these findings.     

Pharmacological basis of therapy with molsidomine

This paper is a synopsis on recent reports dealing with the pharmacological basis of molsidomine-induced circulatory effects. The therapy of coronary insufficiency by molsidomine is based on different pathophysiological and pharmacological mechanisms. The inactive compound molsidomine is metabolized--mainly in the liver--to form the vasoactive and antiaggregatory compound SIN-1 and SIN-1A. Due to the gradual conversion into the active compound, the peak effects are observed only after 15 min (intravenously) or 30 to 60 min (orally). The effects are long-lasting and can be observed up to four to six hours. The c-GMP mediated dilation of various vascular sites comprise mainly the venous system (both small and large veins), resulting in a significant preload reduction, a decrease in cardiac output, a decrease in heart size and circumferential wall stress, a decrease in myocardial oxygen consumption and a therapeutically important improvement of O2-delivery versus myocardial O2-consumption. This effect results in a significant improvement of myocardial ischemia (reducing frequency of anginal attacks, improvement of exercise tolerance and of exercise induced ST-depressions). In animal experiments molsidomine diminishes infarct size and suppresses reperfusion-induced ventricular fibrillation following ischemia. Molsidomine dilates, like nitroglycerin, the large coronary arteries. Therefore, in coronary heart disease, it may improve collateral flow in addition to beneficial effects on subendocardial perfusion resulting from the reduction of ventricular wall stress. In addition to direct dilating effects on collateral vessels an improvement in perfusion of asynergistically contracting ventricular sections has been observed. In contrast to nitroglycerin, effects on peripheral resistance appear only under extremely high dosages and reflex increases in heart rate are rarely observed. In general molsidomine-induced changes (increases) in heart rate, in stroke volume (decreases), and in cardiac output (decreases) are of small magnitude. Recently interesting findings on molsidomine-induced suppression of thrombocyte aggregation, of thromboxan-synthesis inhibition and of increased prostacyclin formation have been presented, which may be important in the improvement of myocardial (micro-) circulation under ischemic conditions.     

Myocardial infarction management with peripheral streptokinase

The early management of myocardial infarction (MI) is undergoing a new evolution. Aggressive treatment and new invasive modalities have brought improved prognosis to these patients. Intracoronary administration of fibrinolytic agents is rapidly gaining wide acceptance. We report a pilot protocol for administration of peripheral intravenous (IV) versus direct intracoronary fibrinolytic agents in acute MI. Thirty patients with acute evolving MI were assigned consecutively to receive fibrinolytic therapy; 15 patients received intracoronary streptokinase and 15 received peripheral IV streptokinase at a dosage of 1.5 million units over a 30-minute period. Evaluation by clinical symptoms, ECG changes, and hemodynamic studies by angiography and radionuclide ventriculography indicated comparable and beneficial results for both groups. Patients assigned to the IV therapy were able to receive streptokinase therapy 1.5 hours earlier than those receiving intracoronary therapy, and they had a higher incidence of reperfusion. We conclude that IV streptokinase therapy may be preferable to intracoronary therapy in view of a higher reperfusion frequency, fewer complications, and greater ease of administration. With both treatment modalities, comparable improvement in left ventricular function was noted. Institutions that do not have invasive techniques available may well be the first to benefit from this method of myocardial salvage, and we encourage cooperation between emergency and cardiology departments.     

Nitroglycerin-resistant coronary spasm treated with intracoronary linsidomine chlorhydrate (SIN-1)

Spontaneous left anterior descending coronary artery spasm occurred in two patients during coronary angiography. After intravenous injection of 0.75 mg of nitroglycerin, the narrowing was unchanged in one patient and only partially relieved in the other. The coronary narrowing completely disappeared after intracoronary injection of 1 mg of the active metabolite of molsidomine, linsidomine chlorhydrate (SIN-1). In the first patient, this injection was performed just prior to the initiation of coronary balloon dilatation, which was then cancelled. Although rare, these two observations demonstrate the limitations of the intravenous use of nitroglycerin during diagnostic coronary angiography and point out the efficacy of intracoronary administration of SIN-1.     

Exercise-induced angina alleviated by intracoronary SIN-1

To investigate the mechanism of action of nitrovasodilators in exercise-induced angina, 15 patients with chronic stable angina underwent a symptom-limited supine exercise test (exercise 1). After recovery, in 10 patients (group I) a coronary vasodilator, SIN-1 (the active metabolite of molsidomine) was injected into the most diseased coronary artery (80 micrograms in 4 min). In the remaining 5, a placebo was injected (group II). Immediately thereafter, the same exercise (exercise 2, identical workloads and exercise duration) was repeated. In group I, after intracoronary injection of SIN-1, the control values at rest (including pulmonary wedge pressure) did not significantly change. Heart rate, blood pressure and cardiac index rose in a similar way during exercises 1 and 2 (61, 20, 26 and 62, 21, 35%, respectively). However, 3 patients were angina-free without ST-changes during exercise 2. In the remaining 7, the ST/heart rate slope was reduced (60%; p less than 0.02), the increase in pulmonary wedge pressure was less pronounced (p less than 0.01) and ST-depression at end-exercise 2 was smaller: 1.3 +/- 0.3 versus 2.1 +/- 0.3 mm (p less than 0.01) for identical work loads and double products. In group II, exercise 2 was identical to exercise 1 and the ST/heart rate slopes were quite reproducible. Therefore, these results argue for an improvement in coronary blood supply after intracoronary SIN-1 and suggest that the beneficial action of nitrovasodilators could be related to direct effects on the coronary circulation. However, the magnitude of this mechanism seems variable from one patient to another.     

直接经皮冠状动脉腔内成形术中冠状动脉内心电图判定存活心肌的价值

目的 应用99mTc-MIBI心肌断层显像(SPECT)评价冠状动脉内心电图(IC-ECG)判定急性心肌梗死(AMI)存活心肌的价值。方法 56例急性前壁心肌梗死患者，接受了直接经皮冠状动脉腔内成形术(PTCA)，梗死相关动脉前降支(LAD)达到TIMI3级血流后IC-ECG自PTCA导引导丝尾端引出作为参照基线，在进一步球囊扩张时IC-ECG ST段再次抬高大于0．2mV时认为具有判定梗死相关部位有存活心肌的意义。测定并比较急性期及恢复期左心室梗死相关区域节段性缩短率(LVSS)与射血分数(LVEF)，梗死区域存活心肌通过恢复早期静息与硝酸甘油介入两次99mTc-MIBI SPECT量化判定。结果 4l例病人(A组)行直接PTCA时IC-ECG ST段明显抬高，15例(B组)未出现相应变化，A组INSS、INEF。在恢复期均显著大于B组，两次99mTc-MIBISPECT显示，硝酸甘油介入后显像A组梗死缺损区面积明显减少，核素放射性计数百分比亦明显增加，B组则无明显改变，说明A组梗死区域有较多存活心肌，与IC-ECT ST段抬高意义一致。结论 直接PTCA过程中可通过球囊扩张时IC-ECG ST段抬高变化初步判定梗死相关区域的心肌活性。     

Analysis of reported randomized trials of streptokinase therapy for acute myocardial infarction in the 1980s

Trials of intracoronary (IC) and intravenous (IV) streptokinase (SK) therapy for myocardial infarction have shown variable effects on mortality and left ventricular (LV) function. A pooled analysis of 10 randomized trials involving a total of 14,355 patients was performed to look for overall trends in the change in mortality within 6 weeks (group A) and after 6 weeks (group B) of follow-up, and the change in LV function. All 10 trials, 7 with IC and 3 with IV SK, were randomized after 1980. There was a significant reduction in mortality risk in patients in group A treated with IV SK (pooled odds ratio = 0.81, 95% confidence interval = 0.73 to 0.90, p less than 0.001). In contrast, no significant differences in mortality were detected in patients in group B treated with IV SK or in patients in either group treated with IC SK. Two IV SK trials that prospectively stratified patient population according to duration of symptoms showed a greater reduction in mortality with administration of SK therapy within 3 hours of onset of symptoms. Analysis of LV function was performed before, within 96 hours after and 1 to 4 weeks after SK therapy. Only 2 of 7 IC SK trials showed significantly greater improvement in global LV ejection fraction in SK group compared with a control group, both showing improvement in LV function between early and late after treatment. Thus, IV SK therapy significantly reduces short-term risk of death after acute myocardial infarction; 2 trials show a greater reduction in mortality risk with earlier institution of IV SK therapy.     

冠状动脉内心电图的研究进展

本文介绍了40年以来冠状动脉内心电图(IC ECG)的简要发展史,主要基于血流储备分数(FFR)对心肌缺血的生理意义,回顾近年来IC ECG与FFR的相关性研究,提出IC ECG相较于FFR的优势,阐明IC ECG的临床应用价值。     

Peroxynitrite alters the catalytic activity of rodent liver proteasome in vitro and in vivo

The proteasome is an important multicatalytic enzyme complex that degrades misfolded and oxidized proteins, signal transduction factors, and antigenic peptides for presentation. We investigated the in vitro effects of peroxynitrite (PN) on the peptidase activity of both crude 20S and 26S and purified 20S proteasome preparations from rat liver as well as proteasome activity in Hep G2 cells and in mouse liver. Crude and purified proteasome preparations were exposed to PN or to the PN donor, 3-morpholinosydnonimine hydrochloride (SIN-1), and then assayed for chymotrypsin-like activity. For in vivo experiments, mice were treated with molsidomine, which is metabolized to SIN-1 in liver. PN and SIN-1 dose-dependently modulated the chymotrypsin-like activity of the 20S proteasome: lower concentrations enhanced proteasome activity, and higher concentrations caused its decline. The NO donor S-nitroso-N-acetylpenicillamine (SNAP), at all concentrations, suppressed 20S proteasome activity. We observed similar results when liver soluble fractions (S-100) were treated with PN, SIN-1, or SNAP, except that enzyme activity in S-100 fractions was less sensitive than the purified enzymes to these agents. Treatment of Hep G2 cells with 0.01 or 0.1 mmol/L SIN-1 stimulated in situ proteasome activity in these cells, while 1 mmol/L SIN-1 suppressed it. SNAP treatment did not affect proteasome activity in Hep G2 cells. Mice treated with molsidomine had enhanced liver proteasome activity 6 hours after treatment, but after 24 hours enzyme activity declined below control levels. In conclusion, PN dose-dependently modulated proteasome activity, regulating protein degradation by the proteasome in liver cells.     

Prediction of the lower esophageal sphincter pressure after oral molsidomine by sydnonimine plasma concentrations.

BACKGROUND/AIMS: Recent studies suggest that endogenous nitric oxide decreases lower esophageal sphincter pressure (LESP). Substances leading to the formation of nitric oxide, such as molsidomine, decreases the human LESP. It is not yet clear whether this reduction is related to plasma concentrations of molsidomine, the nitrate-active substance sydnonimine (SIN-1) or to serum concentrations of nitrate/nitrite (NOx) as a stable end-product of volatile nitric oxide. METHODOLOGY: We performed a double blind controlled crossover trial in 8 healthy male volunteers. Plasma concentrations of molsidomine, SIN-1 and serum concentrations of NOx as well as esophageal manometry were determined. RESULTS: Mean basal LESP was significantly decreased from 25.4 +/- 2.8 mmHg to 21.9 +/- 2.7 mmHg and 21.4 +/- 2.6 mmHg 2 and 3 hours after molsidomine administration, respectively (mean +/- SEM; n = 8; p < 0.05). The maximum decrease of LESP from the baseline within 1-4 hours after molsidomine administration was 7.6 +/- 1.5 mmHg (mean +/- SEM; n = 8; p < 0.01). The decrease of the LESP correlated significantly with plasma concentrations of SIN-1 (r = -0.53; p = 0.002). NOx levels remained unchanged. CONCLUSIONS: Molsidomine decreases the LESP and plasma concentrations of the active metabolite SIN-1 may predict the potency of molsidomine to lower LESP. NOx was useless as a control metabolite to measure the LESP in response to molsidomine in healthy volunteers.     

Molsidomine

Molsidomine is an established drug for the treatment of coronary heart disease. It acts via the metabolite SIN-1 through liberation of NO. Experiments have proven the identity of NO and EDRF. Investigation of the molecular mechanism of action of molsidomine/SIN-1 indicate that molecular oxygen initiates NO formation through a one-electron abstraction from the intermediate. Ex vivo experiments in rats and in vitro studies in human coronary arteries showed that marked tolerance is induced with glyceryl trinitrate, whereas prolonged exposure to SIN-1 does not cause tolerance. Responsiveness to SIN-1 is not modified in nitrate-tolerant human arteries. Stimulation of soluble guanylate cyclase underlies the antiaggregatory actions of EDRF. Likewise SIN-1 inhibits platelet aggregation in various models. In dogs and pigs with critical stenosis molsidomine reduced significantly the frequency and the severity of cyclical reductions of coronary blood flow.     

急性ST段抬高型心肌梗死围手术期替罗非班不同给药方法的研究

目的探讨导管室内经下游冠状动脉和上游静脉内注射负荷剂量替罗非班对血管造影结果和左室功能的影响。方法连续入选210例急性ST段抬高型心肌梗死行直接PCI的患者,分为上游静脉组（105例,在急诊室经静脉注射负荷剂量的替罗非班10μg／kg）和下游冠状动脉组（105例,在导管室完成诊断性造影之后经指引导管冠状动脉内注射替罗非班10μg／kg）。两组患者均后续以0．15μg·kg^-1·min^-1静脉泵入替罗非班36h。观察指标包括：手术前、后TIMI（TIMI）血流分级,校正TIMI计帧数（cTFC）,心肌灌注分级（MBG）。术后1个月使用超声心动图评价左室功能恢复情况。结果上游静脉组各个初始造影指标均明显优于下游冠状动脉组,TIMI3级血流24％比10％,P=0．01;cTFC（78±30）比（92±21）,P=0．001;MBG2或3级15％比6％,P=0．02。而术后心肌水平灌注指标下游冠状动脉组均明显优于上游静脉组,ST段回落〉70％的比率50％比35％,P=0．03;MBG2或3级79％比58％,P=0．01。左室功能恢复指标显示下游冠状动脉组明显优于上游静脉组,EF平均增加（8±7）％比（6±7）％,P=0．02;室壁运动分数指数平均增加（0．4±0.3）比（0.3±0．3）,P=0．03。结论行直接经皮冠状动脉介入治疗的ST段抬高型急性心肌梗死患者,在导管室经冠状动脉注射替罗非班,可以改善介入术后的心肌组织水平灌注和术后1个月时左室功能的恢复。这可能得益于冠状动脉内局部注射,使病变局部及病变远端的血管床有较高的药物浓度。     

A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction.

AIMS: Mesenchymal stem cells (MSCs), rare bone marrow-derived stem cell precursors of non-haematopoietic tissues, have shown promise in potentially repairing infarcted myocardium. These and similar cell types are being tested clinically, but understanding of delivery and subsequent biodistribution is lacking. This study was designed to quantitatively compare MSC engraftment rates after intravenous (IV), intracoronary (IC), or endocardial (EC) delivery in a porcine myocardial infarction (MI) model. METHODS AND RESULTS: Allogeneic, male MSCs were cultured from porcine bone marrow aspirates. Iridium nanoparticles were added during culturing and internalized by the MSCs. An MI was induced in female swine (27-40 kg in size) by prolonged balloon occlusion of the mid-left anterior descending artery. Animals (n = 6 per group) were randomized to one of three delivery methods. Cellular engraftment was determined 14+/-3 days post-delivery by measuring ex-vivo the iridium nanoparticle concentration in the infarct. Confirmation of cellular engraftment utilized both DiI and fluorescence in situ hybridization (FISH) labelling techniques. During MSC infusion, no adverse events were noted. However, following IC infusion, half of the pigs exhibited decreased blood flow distal to the infusion site. At 14 days, the mean number of engrafted cells within the infarct zone was significantly greater (P< or =0.01) following IC infusion than either EC injection or IV infusion and EC engraftment was greater than IV engraftment (P< or =0.01). There was less systemic delivery to the lungs following [EC vs. IV (P = 0.02), EC vs. IC (P = 0.06)]. Both DiI and FISH labelling demonstrated the presence of engrafted male MSCs within the female infarcted tissue. CONCLUSION: IC and EC injection of MSCs post-MI resulted in increased engraftment within infarcted tissue when compared with IV infusion, and IC was more efficient than EC. However, IC delivery was also associated with a higher incidence of decreased coronary blood flow. EC delivery into acutely infarcted myocardial tissue was safe and well tolerated and was associated with decreased remote organ engraftment with compared with IC and IV deliveries.     

Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-Week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) study

Objectives. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was initiated to determine the feasibility of a large trial in evaluating the effects of treatment of ischemia on outcome (mortality and myocardial infarction). The study was designed to examine the effects of medical treatment to control angina compared with treatment strategies guided by ambulatory electrocardiographic (ECG) ischemia or coronary anatomy.Background. Treatments to suppress ischemia (asymptomatic and symptomatic) have not been evaluated in a large prospective, randomized trial. Before undertaking such a trial, issues about recruitment and treatment strategies must be addressed.Methods. The 618 enrolled patients had coronary artery disease suitable for revascularization, ischemia on stress test and asymptomatic ischemia on ambulatory ECG. Patients were assigned randomly to one of three treatment strategies: 1) angina-guided medical strategy with titration of anti-ischemic medication to relieve angina (angina-guided strategy); 2) angina-guided plus ambulatory ECG ischemia-guided medical strategy with titration of anti-ischemic medication to eliminate both angina and ambulatory ECG ischemia (ischemia-guided strategy); and 3) revascularization by angioplasty or bypass surgery (revascularization strategy).Results. Ambulatory ECG ischemia was no longer present at the week 12 visit in 39% of patients assigned to the angina-guided strategy, 41% of patients assigned to the ischemia-guided strategy and 55% of patients assigned to the revascularization strategy. All strategies reduced the median number of episodes and total duration of ST segment depression during follow-up ambulatory ECG monitoring. Revascularization was the most effective strategy. Treadmill test results were concordant with those of ambulatory ECG monitoring, lor most patients in the two medical strategies, angina was controlled with low to moderate doses of anti-ischemic medication, and the majority of patients (65%) in the revascularization strategy did not require medication for angina.Conclusions. This pilot study demonstrated that cardiac ischemia can be suppressed in 40% to 55% of patients with either low or moderate doses of medication or revascularization and that a large trial is feasible.     

Meta-analysis of prospective randomized controlled trials comparing intracoronary versus intravenous abciximab in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Abciximab is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to improve outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention (pPCI). An earlier study reported better efficacy with intracoronary (IC) compared to intravenous (IV) administration, but this finding has not been duplicated in other studies, thus leaving a great deal of uncertainty as to the most efficacious route of administration. To investigate if IC abciximab compared to IV administration decreases mortality and major adverse cardiac events in patients with ST-segment elevation myocardial infarction who undergo pPCI, a meta-analysis was performed consisting only of prospective randomized controlled trials. Subgroup analysis was performed to investigate the source of difference in efficacy between the 2 strategies. A meta-analysis of 4 trials including 1,148 subjects revealed that IC abciximab significantly reduced mortality compared to IV administration (1.5% vs 3.6%, odds ratio 0.44, 95% confidence interval 0.20 to 0.95, p = 0.04). Major adverse cardiac events were also reduced in a subgroup in which <30% of patients received aspiration thrombectomy (6.1% vs 16.2%, odds ratio 0.33, 95% confidence interval 0.18 to 0.61, p = 0.0004). In conclusion, the totality of the data available from relatively small but high-quality studies shows a significant mortality reduction associated using IC abciximab for pPCI compared to IV abciximab. IC abciximab in the setting of pPCI for ST-segment elevation myocardial infarction may be beneficial for patients with higher risk profiles.     

Mechanisms of abnormal Q waves in hypertrophic cardiomyopathy assessed by intracoronary electrocardiography

INTRODUCTION: To clarify the mechanisms of abnormal Q waves in hypertrophic cardiomyopathy (HCM), local epicardial electrical activities were assessed by intracoronary electrocardiography (ECG). METHODS AND RESULTS: Unipolar intracoronary ECG was recorded by introducing a guide wire for angioplasty into the left anterior descending artery (LAD) in 20 patients with HCM and 10 control subjects. Intracoronary ECG showed no Q waves in any control subjects. Intracoronary ECG showed no Q waves in 8 HCM patients without abnormal Q waves on surface ECG. In 12 HCM patients with abnormal Q waves on surface ECG, 4 showed Q waves on intracoronary ECG associated with regional wall-motion abnormalities, suggesting Q waves are formed by loss of electrical forces due to transmural myocardial fibrosis. The remaining 8 patients, who did not have Q waves on intracoronary ECG, showed greater thickening of the basal free wall than the apical free wall, with no wall-motion abnormalities. Intracoronary ECG was characterized by increased R or R' waves and prolonged R peak times at the proximal LAD, suggesting Q waves are formed by increased electrical forces of hypertrophied basal septal and/or ventricular free wall, unopposed by apical forces. CONCLUSION: The study findings provide evidence for two mechanisms of abnormal Q waves in HCM: (1) loss of electrical forces due to transmural myocardial fibrosis, and (2) altered direction of resultant initial QRS vector due to increased electrical forces of disproportionate hypertrophy of the basal septal and/or ventricular free wall, unopposed by apical forces.     

Usefulness of intracoronary isosorbide dinitrate in alleviating myocardial ischaemia during coronary balloon angioplasty.

The effect of intracoronary isosorbide dinitrate on provoked myocardial ischaemia during percutaneous transluminal coronary angioplasty (PTCA) was studied in 60 patients who had at least 1 mm electrocardiographic (ECG) ST segment deviation during a 70 s control balloon inflation period. Isosorbide dinitrate (dose 1 mg, 2 mg or 3 mg) or placebo (saline) was administered by slow intracoronary injection, and the ST segment changes recorded again during an identical dilatation period 2-4 min later. Following injection of isosorbide dinitrate, the severity of ST segment deviation decreased (1 mg -31 +/- 30%, P = 0.03; 2 mg -51 +/- 35%, P = 0.0001; 3 mg -36 +/- 32%, P = 0.002) during coronary balloon inflation, and the time until onset of 1 mm ST deviation was prolonged (1 mg +79 +/- 137%, P = 0.06; 2 mg +85 +/- 87%, P = 0.02; 3 mg +78 +/- 109%, P = 0.02). With the 3 mg dose, the time to maximum ECG change increased (+37 +/- 87%, P = 0.02). In the placebo group, there was a small decrease in the severity of ST segment deviation in patients receiving placebo (-23 +/- 32%, P = 0.03), but no change in the time to its onset or in the time to maximum ST deviation. Isosorbide dinitrate did not alter heart rate, systolic arterial pressure or the rate-pressure product at maximum ST segment change, implying that when isosorbide was administered by direct intracoronary injection, a direct cardiac effect was responsible for the major anti-ischaemic effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

冠状动脉内应用国产替罗非班对急性ST段抬高心肌梗死急诊介入治疗后心肌灌注和临床预后的影响

目的 探讨急性ST段抬高心肌梗死急诊PCI时国产替罗非班的不同应用途径（静脉内／冠状动脉内）对心肌组织水平灌注与临床预后影响的差异。方法 连续选择60例急性ST段抬高心肌梗死拟行急诊PCI的患者,随机分为替罗非班静脉内应用组（静脉组,n=30）与替罗非班冠状动脉内应用组（冠状动脉组,n=30）,比较两组术后即刻造影结果、住院期间以及随访期间主要不良心脏事件（MACE）发生的差异。结果共有54例完成试验,其中男性43例,女性11例,年龄29～75（58．80±12．57）岁,冠状动脉组在术后心外膜TIMI分级、TIMI心肌灌注分级（TIMI Myocardial Perfusion,TMP）、心电图ST段回落、梗死相关血管远端末梢栓塞、以及治疗后5～7天的心脏彩超射血分数值、左室舒张末期容积（LVEDV）、左室收缩末期容积（LVESV）等方面均显著优于静脉组,虽然心脏肌钙蛋白I（cTnI）与肌酸激酶同工酶（CK-MB）峰值浓度两组无差异,但是冠状动脉组CK-MB达峰值的时间显著缩短,两组院内MACE事件发生未达到统计学差异,平均住院日亦相同,但是30～90（平均57±21）天随访期间冠状动脉组总的MACE事件发生显著少于静脉组（7．1％与30．8％,P=0．02）。应用Cox回归比例风险模型在校正年龄、性别、高血压、糖尿病、家族史、吸烟等危险因素以及心肌梗死部位、胸痛至球囊扩张时间后,计算冠状动脉组在平均57天随访期间发生总的MACE事件的相对危险度为0．14（P=0．03）。冠状动脉组发生轻度出血与严重出血并发症有增多的趋势,但未达到统计学差异。结论 对于急性ST段抬高心肌梗死行急诊PCI治疗的患者,冠状动脉内应用替罗非班安全、有效,与静脉内应用相比可以进一步改善心肌水平再灌注状态并能提高临床预后,这对于在急诊室因为各种原因未能提前应用替罗非班的患者来说具有特殊的临床意义。     

Feasibility and safety of regional myocardial hypothermia during myocardial ischemia and infarction in pigs

OBJECTIVE: Mild systemic hypothermia has been shown to be feasible and safe in patients during acute myocardial infarction (AMI). Regional myocardial hypothermia of the ischemic myocardium only may be more effective in myocardial salvage with fewer side effects compared with systemic hypothermia. The purpose of this study was to evaluate the feasibility and safety of regional myocardial hypothermia in pigs. METHODS: Open-chest pigs with (n=5) or without (n=4) myocardial infarction underwent left anterior descending coronary artery (LAD) ligation followed by intracoronary infusion of lactated Ringer's solution (at room temperature and at 15 degrees C between 20-35 ml/min for 3 min) via the central lumen of a specially designed balloon catheter at the time of reperfusion. Intramyocardial temperatures via thermocouples at the ischemic zone (LAD territory) and non-ischemic zone (circumflex territory) as well as systemic temperature were constantly recorded, as were the hemodynamics. Each pig acted as its control regarding the myocardial temperature response to both solutions. In addition, intracoronary versus intramyocardial temperatures were compared with thermocouples in both territories during infusion. RESULTS: There was no hemodynamic compromise or arrhythmia seen during the intracoronary infusion of either temperature solution. There was a linear relationship between the infusion solution temperature and infusion rate versus intramyocardial temperature response, with the cooled solution providing 2 degrees C lower temperature and faster infusion resulting in lower intramyocardial temperature. There was no change in the non-ischemic zone or systemic temperature. On average, 6-8 degrees C reduction in tissue temperature, potential target temperature range for hypothermic therapy, was achieved in all animals. In addition, intracoronary temperature in distal LAD measured by intracoronary thermocouples correlated with the intramyocardial temperature (2 degrees C lower temperature in the coronary artery). CONCLUSION: It is feasible and safe to achieve regional myocardial hypothermia by intracoronary infusion of cooled solution in pigs.     

Pretreatment with intracoronary enalaprilat protects human myocardium during percutaneous coronary angioplasty.

OBJECTIVES: We tested the hypothesis that enalaprilat induces preconditioning (PC)-mimetic actions in patients with stable coronary artery disease. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors increase the bioavailability of bradykinin, which induces cardiac PC. METHODS: Twenty-two patients undergoing coronary angioplasty were randomized to an intracoronary infusion of enalaprilat or placebo, followed 10 min later by a PC protocol. RESULTS: In control patients, the ST-segment shift was greater during the first inflation than during the second and third inflations, both on the intracoronary electrocardiogram (ECG) (21.0 +/- 2.8 mm vs. 13.0 +/- 2.0 mm and 13.0 +/- 2.0 mm, p < 0.05) and the surface ECG (16.0 +/- 4.0 mm vs. 10.0 +/- 2.0 mm and 9.0 +/- 2.0 mm, p < 0.05). In contrast, enalaprilat-pretreated patients showed no change in ST-segment shift during inflations on either the intracoronary or the surface ECG. During the first inflation, the ST-segment shift was significantly smaller in treated versus control patients. The chest pain score during the first inflation was also significantly smaller in treated patients versus control patients (33.0 +/- 6.0 mm vs. 64.0 +/- 6.0 mm) and did not change in treated patients during the second and third inflations, whereas it decreased significantly in control patients. In a subset of 6 patients, enalaprilat increased coronary blood flow during infusion, but this effect dissipated before the beginning of angioplasty. CONCLUSIONS: Pretreatment with enalaprilat attenuates the manifestations of myocardial ischemia during angioplasty. This is the first in vivo evidence showing that an ACE inhibitor protects human myocardium, possibly via PC-mimetics actions, a novel property that might explain the cardioprotective actions of these drugs.